The present invention relates generally to the field of protein crystallization analysis and in particular to a process and apparatus for capturing, indexing, analyzing and storing images of protein crystallization samples.
Protein crystallization is a technique used to analyze the molecular structure of proteins. In this technique, varying controlled ratios and combinations of certain chemical reactants or catalysts are added to a protein sample or “drop” to induce the protein to crystallize so that its structure may be analyzed for use in biochemical research applications.
As shown in FIG. 1, one type of crystallization plate 2 includes a number of cells, each cell 4 having a number of satellite wells (three in the example). The cells are identified by row and column number, such as Al, B10, etc., and each satellite well is identified by its position number in the cell (such as 1, 2 or 3). A quantity of a protein is placed into each of the satellite wells, and a different experimental amount of a crystallization catalyst is added to each satellite well in an attempt to induce crystallization of the protein. The mixture is given a sufficient time to react, and then the satellite wells must be viewed under a microscope to determine if sufficient crystallization has occurred. The particular amounts and/or ratios of crystallization catalyst material and protein placed in each satellite well must be recorded in order to determine which ratios and combinations are successful in producing crystallizations. Typically, one protein will be used for each plate, and different catalysts and ratios of catalysts will be added to the protein drops in each satellite well.
Achieving successful protein crystallization is very time consuming and tedious, as only a very small number of crystallizations of a protein occur for many tens or hundreds of thousands of experimental reactant ratios and combinations. Additionally, the contents of a well may be more complex than a simple crystal structure. Specifically, the protein sample (drop) may be turbid as opposed to clear, there may be micro-crystal fields in the sample, protein may be aggregated, and crystals may be embedded in a precipitate field. Since each of these possibilities requires specialized lighting conditions in order to be detected, it is necessary to take many different pictures of the same well under different lighting and focus conditions, thus adding even more complexity to the analysis process.
Accordingly, there is a need for improvement in obtaining, analyzing, and storing protein crystallization experiment images whereby all potential information in an experiment well can be captured quickly and efficiently, and stored together with all experimental parameters and conditions associated with the well.